Chronic pancreatitis with polycystic kidney disease: A rare coincidence?

INTRODUCTION: In children, chronic pancreatitis (CP) is usually associated with anatomical anomalies of the pancreas and biliary tract or is genetically determined. Autosomal dominant polycystic kidney disease (ADPKD) may present with extrarenal cyst formation, sometimes involving the pancreas. Large enough, these cysts may cause pancreatitis in ADPKD patients. CASE PRESENTATION: Herein, we present a case of a 12-year-old Caucasian girl with recurrent pancreatitis with no identifiable traumatic, metabolic, infectious, drug, or immunologic causes. Structural anomalies of the pancreas, including cysts, were ruled out by imaging. However, bilateral cystic kidneys were found as an incidental finding. Her family history was negative for pancreatitis, but positive for polycystic kidney disease. Molecular analysis of ADPKD-causing mutations revealed a novel c.9659C>A (p.Ser3220*) mutation in the PKD1 gene confirming the clinical suspicion of ADPKD. Although CP may rarely occur as an extrarenal manifestation of ADPKD with pancreatic cysts, it is unusual in their absence. Thus, molecular analysis of pancreatitis susceptibility genes was performed and a homozygous pathologic c.180C>T (p.G60=) variant of the CTRC gene, known to increase the risk of CP, was confirmed. CONCLUSION: This is the first reported case of a pediatric patient with coincidence of genetically determined CP and ADPKD. Occurrence of pancreatitis in children with ADPKD without pancreatic cysts warrants further investigation of CP causing mutations.

Chronic pancreatitis associated with the p.G208A variant of PRSS1 gene in a European patient.

CONTEXT: The major etiologic factor of chronic pancreatitis in adults is excessive alcohol consumption, whereas among children structural anomalies, systemic and metabolic disorders, and genetic factors are prevalent. Mutations in the cationic trypsinogen gene (PRSS1) cause hereditary pancreatitis, while mutations in serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR) and chymotrypsin C (CTRC) genes have been shown to associate with chronic pancreatitis as independent risk factors. CASE REPORT: We present a case of 13-year-old boy with idiopathic chronic pancreatitis. Given the unexplained attacks of pancreatitis since early childhood and despite the negative family history, molecular-genetic analysis of four pancreatitis susceptibility genes (PRSS1, SPINK1, CTRC and CFTR) was performed. The boy was found to carry the c.623G>C (p.G208A) mutation of the PRSS1 gene and the c.180C>T (p.G60G) mutation of the CTRC gene, both in heterozygous state. These mutations are considered as contributing risk factors for chronic pancreatitis. CONCLUSIONS: In children with idiopathic chronic pancreatitis genetic causes should be considered, even in absence of positive family history. To the best of our knowledge, this is the first description of a European patient with chronic pancreatitis associated with the p.G208A mutation of PRSS1 gene. This mutation was previously reported only in Asian subjects and is thought to be a unique genetic cause of pancreatitis in Asia.

Thiopurine S-Methyltransferase gene polymorphisms in a healthy Slovak population and pediatric patients with inflammatory bowel disease.

Thiopurine methyltransferase (TPMT) is a key component in thiopurine metabolism. There is an insufficient evidence about the distribution of the genotype frequencies of TPMT variants and frequencies of TPMT alleles associated with intermediate and deficient activity in a healthy Slovak population and pediatric patients with inflammatory bowel disease (IBD). TPMT variant alleles (*1,*2, *3A, *3B, and *3C) were determined in 114 children treated for IBD and in 281 healthy volunteers. Mutant alleles were present in 9/114 (7.89%) in the IBD patients and in 23/281 (8.19%) of probands. The distribution of the most frequent variants of TPMT gene was similar in a healthy population and patients with IBD.

Seasonality of births and childhood inflammatory bowel disease.

PURPOSE: In some geographical areas, including Slovakia, children with diabetes mellitus type 1 are born more often in summer than in late autumn and winter. Does this also apply to another autoimmune disorder - inflammatory bowel disease - in Slovakia? BASIC PROCEDURES: The month of birth was recorded for 30 boys and 36 girls with Crohn disease and 23 boys and 40 girls with ulcerative colitis. The monthly numbers of births were adapted to the length of the given month, divided by the number of boys or girls born in the whole Slovak children population in the same calendar month in comparable years, transformed to moving averages from three successive values each, and expressed as the fraction of the yearly total, which was equal to 1. According to the null hypothesis, there should be equal probability (1/12) of being born in any month. The significance of departures from this value was evaluated with cosinor regression using two sinusoidal functions with period lengths of 12 and 6 months. The most illustrative measure is the relation of the corridor of 95% confidence for the total approximating function to the midline estimating statistic of rhythm (the mesor) (1/12). Significant departures up or down are recognized as nonoverlapping of the mesor straight line by the confidence corridor. MAIN FINDINGS: These were similar to those reported for childhood diabetes mellitus type 1. In our sample of Crohn disease, the number of births was markedly higher between June and October and lower between December and March. In ulcerative colitis, there was a slight increase between June and August and a decrease between December and February. PRINCIPAL CONCLUSIONS: The seasonal effect on births of children with later childhood-onset Crohn disease is similar to that described for diabetes mellitus type 1, i.e., maximal frequency of births in summer.